Ioversol was disclosed as a useful nonionic x-ray contrast agent in U.S. Pat. No. 4,396,598. An intermediate in the production of ioversol is 5-amino-N,N'-bis(2,3-diacetoxypropyl)-2,4,6-triiodoisophthalamide (tetraacetate) having the following structure: ##STR1## This compound and its use in producing ioversol are disclosed in U.S. Pat. No. 4,396,598 incorporated herein by reference. Tetraacetate, as disclosed therein, may be produced by acetylating a compound of the following structure: ##STR2## The acetylation is carried out by reacting 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (tetrahydroxy) with acetic anhydride in N,N,-dimethylacetamide (DMAC) using 4-dimethyl-aminopyridine (DMAP) as a catalyst. The incorporated acetates in this reaction serve as blocking groups or agents to prevent any side reactions from occurring during the subsequent synthetic manipulations. Other blocking agents could also be used, such as, but not limited to dihydropyran, methoxymethylene acetal, ethoxymethylene acetal, acetate ester, chloroacetate ester, benzoate ester, benzylidine acetal, isopropylidine acetal, and cyclic carbonate. Upon completion of the reaction, the mixture is diluted with 1,1,2-trichloroethane and extracted with aqueous sodium carbonate solution to produce tetraacetate.
The resulting tetraacetate, in three additional synthetic steps is converted to ioversol, a compound of the following structure: ##STR3##
This procedure used to produce ioversol heretofore required a forced air drying process to remove water from the crystallized tetrahydroxy, which when prepared in the factory usually contains 20 to 30% water after having been centrifuged. The forced air drying process used in this process is slow and labor intensive.
An alternative method that would eliminate the need for the forced air drying process to remove water from the tetrahydroxy prior to use thereof was desired. It is an object of the present invention to meet this need.